Fullerenes have a closed-shell structure consisting of carbon atoms only, and therefore have distinctive properties. Specific examples of the distinctive properties of the fullerenes are that: (1) a π electronic cloud is uniquely delocalized, (2) the fullerene has a high electron affinity, (3) the fullerene has relatively small ionization energy, (4) the fullerene has a high electron accepting capacity, and (5) photoexcitation occurs with visible light. Since the fullerenes have such properties, the fullerenes have been expected to be applicable in a variety of industrial fields, as semiconductor materials, superconductive materials, photoelectric materials, medical materials, cosmetic materials, etc.
For example, in the medical field, use of the fullerenes in photodynamic therapy (hereinafter may be referred to as “PDT”) is under consideration. The PDT is a treatment method for cancer and the like; cancer cells or the like are killed with use of active oxygen generated by irradiating light to a photosensitive substance. More specifically, in the PDT, the photosensitive substance is administered to a diseased area, and the diseased area is then irradiated with light so that the active oxygen is generated in the diseased area. The active oxygen, for example singlet oxygen and hydroxyradical, is produced as a result of a photochemical reaction of water and oxygen. The active oxygen or a radical species generated from the active oxygen inhibit activity and multiplication of the cancer cells in the diseased area, so as to destroy the cancer cells. Ultimately, cells such as the cancer cells or the like are killed. Since the fullerenes have the aforementioned distinctive properties, the fullerenes efficiently generate the active oxygen such as the singlet oxygen by irradiation of light. Thus, the application of the fullerenes have been expected in the PDT.
As described above, the fullerenes have been expected to be applicable in a wide range of industrial fields, including application of the fullerenes in medical materials such as the PDT. In a case where the fullerenes are used for a variety of purposes, the fullerenes often need to be dissolved in an intended solvent. For example, in order to use a fullerene in the PDT, the fullerene need to be dissolved in an aqueous solvent. However, the fullerenes are not soluble in a polar solvent, such as water. Non Patent Literature 1 discloses that it is possible to solubilize the fullerene in water by complexing the fullerene with cyclodextrin; however, a cyclodextrin complex of the fullerene is not suitable for practical use due to its extreme thermal instablility. As such, the fullerenes have a disadvantage in that they are usable only with a certain limitation, despite the expectations for use in various fields as described above. In order to overcome such a disadvantage, solubilization of the fullerenes in the aqueous solvent has been studied.
Examples of techniques of the fullerenes solubilization are those disclosed in Patent Literatures 1 to 4, and Non Patent Literature 2. Patent Literature 1 discloses various furalors in which a hydroxyl group is introduced into a carbon atom of fullerene so as to solubilize a fullerene. Patent Literature 2 discloses that it is possible to solubilize the fullerenes by coating a surface of a metal-incorporating fullerene or a salt thereof with a polysaccharide having a functional group selected from the group consisting of a sulfone group, a ketone group, an amino group, and an alkyl group. Further, Patent Literature 3 discloses a method for solubilizing a fullerene by coating the fullerene with a polymer chain. More specifically, Patent Literature 3 discloses a method for solubilizing a fullerene by encapsulating fullerene in a structure composed of (i) a core, which is a polymer chain segment containing a repeat unit with a tertiary amino group and/or a secondary amino group on its side chain and (ii) a shell, which is a poly(ethylene glycol) chain segment. Furthermore, Patent Literature 4 and Non Patent Literature 2 disclose that it is possible to obtain a C60-incorporated liposome by transferring C60 from a C60-cyclodextrin complex into a liposome (by exchange reaction). More specifically, Patent Literature 4 and Non Patent Literature 2 disclose that it is possible to transfer C60 into a liposome by mixing a C60-cyclodextrin complex into a liposome solution to obtain a mixture and then heating the mixture for 1 to 7 hours with stirring. Moreover, Patent Literature 4 describes that it is possible to solubilize a fullerene through the steps of: preparing a dispersed aqueous solution of the fullerene with use of the fullerene and a dispersion stabilizing agent; and mixing calixarene and the dispersed aqueous solution of the fullerene so as to prepare a complex of calixarene and the fullerene.
Meanwhile, the PDT treats a cancer tissue, in which more water-soluble polymers accumulate than in a normal tissue. The water-soluble polymers once accumulated in the cancer tissue remain for a longer period of time as compared to a case where the water-soluble polymers accumulate in another tissue. Accordingly, when the fullerene is used in the PDT for treating cancer, a fullerene needs not only to be dissolved in an aqueous solvent, but also to be polymerized. Under these circumstances, in order to use the fullerene in the PDT, a technique for polymerizing the fullerene as well as solubilizing the fullerene to an aqueous solvent has been developed. For example, Patent Literature 5 discloses that it is possible to achieve, by chemically-modifying a fullerene with a water-soluble polymer, a solubility of the fullerene to an aqueous solvent as well as an easy transfer of the solubilized fullerene to a cancer tissue.
In addition to the aforementioned technique, a variety of techniques have been disclosed so far for utilizing a fullerene (for example, see Patent Literatures 6 to 9). Patent Literature 6 discloses a new method for stabilizing a diagnostic compound and a therapeutic compound in a cation carrier system. Specifically, Patent Literature 6 discloses a technique that stabilizes, in a cation liposome, a low-molecular-weight compound which has a negative effective charge or a low-molecular-weight compound which is caused to have the negative effective charge due to arbitrary modification. Further, Patent Literature 7 discloses an antioxidant composition and an external composition. Specifically, Patent Literature 7 discloses an antioxidant composition having, as an active constituent, a fullerene included in an organic compound. Furthermore, Patent Literature 8 discloses a technique for solubilizing a fullerene, i.e., a technique for adding higher water solubility to a fullerene. Specifically, Patent Literature 8 discloses a complex of microparticles, which are the fullerenes coated with a polymer chain formed from a certain block copolymer. Patent Literature 9 discloses a photoelectric transducer material in which an electron-accepting compound and an electron-releasing compound respectively form a host-guest complex. Such a complex specifically disclosed in Patent Literature 9 is a complex in which the electron-accepting compound is a fullerene, and the calixarene serves as a host.